Abstract

Aim

Lucitanib is a potent, oral inhibitor of the tyrosine kinase activity of FGFR1/2, VEGFR1-3 and PDGFRα/ß. These well-described signaling pathways are essential for tumor growth, survival, migration, and angiogenesis. Considering the highly vascular nature and the expression of FGFR in thyroid cancer, targeting these pathways is particularly relevant in metastatic setting.

Methods

The first in human phase I/II study is currently evaluating oral lucitanib as monotherapy. The escalation phase used a 3 + 3 design in pts with advanced solid tumors to establish a recommended dose for further study. Safety and efficacy were further evaluated in pts with FGF aberrant or angiogenesis sensitive tumors, using continuous or intermittent dosing schedules.

Results

Among 32 pts treated in Vall d'Hebron Institute of Oncology (VHIO), 3 had medullary thyroid cancer and 6 differentiated thyroid cancer. Median age was 56 yrs [range 38-68]. All pts were treated at 15mg, 5 on continuous and 4 on intermittent schedules (21 days on / 7 days off). 4 pts (45%) received lucitanib after progression on at least one previous multikinase inhibitor (MKI). In this population, the most common adverse events related to lucitanib (all grades, continuous and intermittent dosing schedules) were hypertension, asthenia and proteinuria. For all these AEs, the highest grade observed was G2. All pts on continuous schedule had a dose decrease to 10mg due to drug-related toxicities. 2/4 pts on intermittent schedule maintained on their initial 15mg dosing. The anti-tumor activity was recorded in 8 of the 9 pts evaluable according to RECISTv1.1. One pt achieved CR (12%), 2 pts had PR (25%) including 1 MKI pretreated, and 4 pts had SD (50%) lasting at least 6 months, including 2 pts MKI pretreated. Moreover, 1 pt had a prolonged CR (30 months), evaluable on non-target lesions only. Median PFS was 15.0 months, and 3 pts are still ongoing for more than 28 cycles.

Conclusions

Lucitanib demonstrated promising clinical activity and a torelable side-effect profile in pts with metastatic thyroid cancer even in those already pretreated with multikinase inhibitors.

Disclosure

R. Cereda: Full employment at EOS Spa; J. Litten: Full employment at Clovis; J. Collin, F. Legrand, R. Robert and C. Saba: full employment at Servier. All other authors have declared no conflicts of interest.